Candida albicans is the most common fungal pathogen of humans, and the third or fourth most common microorganism isolated from blood cultures obtained in the U.S.A. C. albicans is a dimorphic fungus that is both a commensal and opportunistic pathogen of man. Depending on the underlying host defect, Candida is able to cause a variety of infections that range from mucosal to life-threatening disseminated candidiasis, having the ability to infect virtually every organ in the host. Predisposing factors for candidiasis include immunosuppressive therapy, massive antibiotic therapy, cytotoxic therapy, intravenous catheters and indwelling devices, very low birth weight, AIDS, diabetes, transplantation medicine, drug dependency, etc. In normal individuals, this organism colonizes the gastrointestinal tract, vagina and some cutaneous areas. Opportunistic superficial and systemic C. albicans infections develop in premature newborns, AIDS and debilitated cancer patients, and are particularly frequent and severe after bone marrow transplantation. These opportunistic infections are believed to have an endogenous origin.
One particular condition arising from an infection of C. albicans is invasive candidiasis which is a major cause of morbidity and mortality in immunocompromised patients. In general, the morhphogenetic conversions between yeast and hyphal growth forms appear to be critical in the pathogenesis of invasive candidiasis and may be regulated by environmental signals such as extracellular pH. Accordingly, most agree that the ability of C. albicans to invade host tissues is largely dependent on the morphogenetic conversions between the yeast and the filamentous forms. Yeast cells and hyphae may encounter different microniches within the host. Besides temperature and serum, extracellular pH is an important environmental cue that regulates the transition between the yeast and the hyphal growth forms.
The extremely severe problems caused by C. albicans, including the lack of an early and accurate diagnostic procedure, the high toxicity exhibited by the most common and effective treatments, and the emergence of resistant strains due to empirical prophylactic treatment, have resulted in very high morbidity and mortality rates associated with disseminated infections. Because of these reasons, there is an increasing interest in the development of preventive strategies and in the search for new or alternative therapies to enhance or complement a multicomponent approach to the management of candidiasis. However, despite the efforts of numerous groups of investigators, our present understanding of the pathogenicity mechanisms of this microorganism, as well as our knowledge of factors determining host susceptibility, are still exploratory areas.
As indicated above, pathogenicity resulting from a yeast infection is also dependent on host-related factors. More importantly, the immunological status of the host seems to be of special relevance for susceptibility to fungal and yeast infections. In the case of C. albicans and other pathogenic fungi, the importance of cellular defense mechanisms for protection is supported by the fact that most invasive manifestations are detected in patients with deficiencies in cellular immunity. Cell-mediated immunity (T cells) and nonspecific cellular immunity (macrophages, neutrophils and NK cells) are generally believed to play important roles in protection against candidiasis. However, the role of humoral immunity in candidiasis and other fungal infections remains a controversial issue, with contradictory reports that either support or deny the importance of antibody immunity.
In any event, it remains a distinct problem in the field of fungal and yeast infections such as invasive candidiasis to develop adequate means of identifying, treating or preventing such infections so as to control such outbreaks, particularly among highly susceptible patients, such as premature newborns, AIDS sufferers, and debilitated cancer patients In particular, it remains a challenge to develop compositions and methods for treating and preventing fungal infections and diseases such as candidiasis caused by Candida microorganisms.